Difference between revisions of "Programmed death-ligand 1"

Programmed death-ligand 1 (view source)

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-'''Programmed death-ligand 1''', commonly abbreviated '''PD-L1''', is protein with an important role in  immune system regulation, and thus [[cancer]] aggressiveness.
+[[Image:PD-L1_positive_lung_adenocarcinoma_--_intermed_mag.jpg|right|thumb|[[Micrograph]] showing a PD-L1 positive non-small cell lung carcinoma (NSCLC). PD-L1 [[immunostain]] (22C3). (WC)]]
+'''Programmed death-ligand 1''', commonly abbreviated '''PD-L1''', is a protein with an important role in immune system regulation and [[cancer]].
+[[Image:PD-L1 negative lung adenocarcinoma -- high mag.jpg|right|thumb|[[Micrograph]] showing a PD-L1 negative [[NSCLC]]. PD-L1 immunostain (22C3). (WC)]]
-It is also known as '''CD274'''.<ref name=omim>{{OMIM|605402}}</ref>
+Normally, PD-L1 on cells binds with [[programmed cell death 1]] on the T lymphocytes.<ref name=pmid22658126/>
+PD-L1 is also known as '''CD274'''.<ref name=omim>{{OMIM|605402}}</ref>
+==General==
+[[Image:PD-L1_positive_lung_adenocarcinoma_in_lymph_node_--_intermed_mag.jpg|thumb|right|PD-L1 positive lung adenocarcinoma in a lymph node. 22C3 PD-L1 immunostain. (WC)]]
+*In theory, positive PD-L1 [[IHC|immunostaining]] predicts response to anti-PD-L1 drugs.<ref name=pmid26970723/>
+**Carcinoma cell is  considered "PD-L1 positive" if the cell membrane is partially or completely stained.<ref name="pmid27389313">{{Cite journal  | last1 = Scheel | first1 = AH. | last2 = Dietel | first2 = M. | last3 = Heukamp | first3 = LC. | last4 = Jöhrens | first4 = K. | last5 = Kirchner | first5 = T. | last6 = Reu | first6 = S. | last7 = Rüschoff | first7 = J. | last8 = Schildhaus | first8 = HU. | last9 = Schirmacher | first9 = P. | title = Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. | journal = Mod Pathol | volume = 29 | issue = 10 | pages = 1165-72 | month = Oct | year = 2016 | doi = 10.1038/modpathol.2016.117 | PMID = 27389313 }}</ref>
+*It is, however, more complex than that. Some tumour types are invariably positive, e.g. classical Hodgkin lymphoma, so testing is unhelpful. In contrast, tumors such as malignant melanoma respond regardless of PD-L1 immunoexpression.
+*The plethora of companion diagnostics developed for each PD-1/ PD-L1 inhibitor has created challenges, as these assays include different IHC antibody clones, staining protocols and platforms, scoring systems, and cutoffs for defining positivity.
+**Nivolumab - 28-8 (Dako)
+**Pembrolizumab - 22C3 (Dako)
+**Aterolizumab -  SP142 (Ventana)
+**Durvalumab -  SP263 (Ventana)
+**Avelumab - 73-10 (Dako)
+===Background===
+Cytotoxic T cell function is regulated by receptor pairs found on the tumour and lymphocyte:<ref name=pmid22658126>{{Cite journal  | last1 = Ribas | first1 = A. | title = Tumor immunotherapy directed at PD-1. | journal = N Engl J Med | volume = 366 | issue = 26 | pages = 2517-9 | month = Jun | year = 2012 | doi = 10.1056/NEJMe1205943 | PMID = 22658126 }}</ref>
+{| class="wikitable sortable"
+! Function
+! Tumour cell
+! T cell
+|-
+| Antigen presentation
+| MHC
+| TCR
+|-
+| Signal inhibition
+| PD-1
+| [[PD-L1]] (CD274), PD-L2 (CD273)
+|}
+==Prognosis==
+*Good prognosis - in high-grade [[ovarian serous carcinoma]], associated with [[tumour-infiltrating lymphocytes]].<ref name=pmid26972336>{{Cite journal  | last1 = Webb | first1 = JR. | last2 = Milne | first2 = K. | last3 = Kroeger | first3 = DR. | last4 = Nelson | first4 = BH. | title = PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer. | journal = Gynecol Oncol | volume = 141 | issue = 2 | pages = 293-302 | month = May | year = 2016 | doi = 10.1016/j.ygyno.2016.03.008 | PMID = 26972336 }}</ref>
+==Drugs - Immune checkpoint inhibitors==
+*PD-1 inhibitors:
+**Nivolumab (''Opdivo'', Bristol-Myers Squibb).
+**Pembrolizumab (''Keytruda'', Merck).
+*PD-L1 inhibitors:
+**Atezolizumab (''Tecentriq'', Roche).<ref name=pmid26970723>{{Cite journal  | last1 = Fehrenbacher | first1 = L. | last2 = Spira | first2 = A. | last3 = Ballinger | first3 = M. | last4 = Kowanetz | first4 = M. | last5 = Vansteenkiste | first5 = J. | last6 = Mazieres | first6 = J. | last7 = Park | first7 = K. | last8 = Smith | first8 = D. | last9 = Artal-Cortes | first9 = A. | title = Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. | journal = Lancet | volume =  | issue =  | pages =  | month = Mar | year = 2016 | doi = 10.1016/S0140-6736(16)00587-0 | PMID = 26970723 }}</ref>
+**Durvalumab (''Imfinzi'', AstraZeneca).
+**Avelumab (''Bavencio'', Merck/Pfizer).
+===Anti-PD-L1 drugs - use===
 PD-L1 antibodies are being used to treat:<ref name=pmid26895815>{{Cite journal  | last1 = Gandini | first1 = S. | last2 = Massi | first2 = D. | last3 = Mandalà | first3 = M. | title = PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis. | journal = Crit Rev Oncol Hematol | volume = 100 | issue =  | pages = 88-98 | month = Apr | year = 2016 | doi = 10.1016/j.critrevonc.2016.02.001 | PMID = 26895815 }}</ref>
 *[[Malignant melanoma]].
 *[[Non-small cell lung cancer]].
+**Associated with response predicted by [[tumour-infiltrating lymphocytes]] and ''PD-L1 IHC'' positivity of the tumour cells.<ref name=pmid26970723/>
 *[[Renal cell carcinoma]].
+*[[Urothelial carcinoma]].
+*[[Merkel cell carcinoma]]
+*[[Acute myeloid leukemia]]
 ==See also==
 *[[Molecular pathology]].
+*[[Cytotoxic T-lymphocyte-associate antigen 4]].
 ==References==

Difference between revisions of "Programmed death-ligand 1"

Programmed death-ligand 1 (view source)

Revision as of 14:25, 19 November 2018

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